tbuckley/cabot-search huggingface dataset:
Abstract 11888: Interplay Between Metabolic Biomarkers, Adipose Tissue Depots and Coronary Artery Disease in the PROMISE Clinical Trial
Authors: Elizabeth Zhao, Stephanie Giamberardino, Neha J Pagidipati, Deepak Voora, Udo Hoffmann, Julia Karady, Maros Ferencik, Borek Foldyna, Pamela S Douglas, Svati H Shah
Journal: Circulation (2022)

Background. Visceral adipose depots such as hepatic steatosis (HS) and epicardial fat (EAT) have been implicated as markers for CVD. Higher BCAA have been implicated in HS progression, but the interplay between BCAA, different adipose tissue depots (ATDs) and CAD has not been evaluated. We leveraged the PROMISE clinical trial with centrally adjudicated coronary CTA imaging to determine relationships between ATDs, BCAA dysregulation and CAD. Methods. The PROMISE trial randomized 10,003 outpatients with stable chest pain to CTA vs. standard of care diagnostics. We included 4,019 participants with available CTA and biospecimens. ATDs (HS [presence/absence] and EAT volume) and CAD were determined by a CT core lab. NMR spectroscopy was used to measure serum BCAA (total). We determined association between (1) BMI and ATDs with obstructive CAD ( &gt; 50% stenosis in a major epicardial coronary vessel); (2) BCAA and ATDs; and (3) BCAA and CAD, using univariate and multivariate regressions. Association between BCAA with time-to-incident CVD events (all-cause death, myocardial infarction, or unstable angina hospitalization) was performed using Cox proportional hazard models. Individual BCAA SNPs were used as the instruments for Mendelian randomization (MR) analyses to evaluate if BCAA are in the casual pathway for HS or CAD. Results. The population had a mean age of 60 years, BMI of 30.8, was 53% female, 27.1% had HS, 13.9% had CAD, and 15.4% had high risk coronary plaque. EAT was associated with CAD in the multivariate models (OR 1.004, 95% CI [1.00-1.01], p=0.019). HS was not associated with CAD. Total BCAA levels were associated with HS in multivariate models (OR 1.46, 95% CI [1.28-1.67], p&lt;0.001), but BCAA were not associated with EAT. BCAA were associated with CAD in univariate (OR 1.18, CI 1.04-1.34, p&lt;0.001), but were not associated with incident events. Mendelian randomization did not support the role of BCAA as in the casual pathway of HS or CAD. Conclusions. Leveraging a large clinical trial, we found that CTA-derived ATDs are associated with CAD. We further established the role of dysregulated BCAA catabolism in HS, although this relationship did not seem to be associated with or in the causal pathway of CAD.
Abstract 12581: The N <sup>6</sup> -Methyladenosine Methylase Wtap is Essential for Cardiac Homeostasis
Authors: Ziqiang Han, Yubao Zou, Shuai Li, Minjie Lu, Yu Nie, lei song, Jizheng Wang
Journal: Circulation (2022)

Introduction: N 6 -methyladenosine (m 6 A) methylation is one of the most common internal modifications in mammalian mRNA, and WTAP is a critical regulatory subunit of the RNA N 6 -methyladenosine methyltransferase complex. However, the roles of WTAP in cardiac structure and function are rarely known. Methods and Results: We found that the levels of m 6 A RNA methylation and the expression of WTAP were both decreased in myocardial tissue of the patients with hypertrophic cardiomyopathy, as well as in pressure overload-induced cardiac hypertrophy in mice. To determine the regulatory roles of WTAP, a conditional cardiac-specific knockout mice of WTAP was generated through Tamoxifen-inducible αMHC-Cre/loxP system. Depletion of WTPA resulted in heart failure in five days after Tamoxifen treatment, shown by enlarged heart and decreased left ventricular ejection fraction. Furthermore, we found WTAP knockout aggravated the progress of pathogenic cardiac remodeling induced by pressure overload, and abrogated the compensated response cardiac hypertrophy to hypertrophic stimulation. We found MYLK4 was a direct target of WTAP through a methylated RNA immunoprecipitation (MeRIP) sequencing, and it was validated by MeRIP-qPCR, RT-qPCR and RIP-qPCR. RNA stability analysis and dual-luciferase assays showed that depression of WTAP decreased m6A level of MYLK4 mRNA and resulted in a down-regulation of MYLK4 by reducing its RNA-stability. Forced overexpression of MYLK4 adeno-associated virus was able to partly alleviate the cardiac dysfunction induced by WTAP deletion. Finally, it was surprising that overexpression of WTAP also promotes pathogenic cardiomyocyte hypertrophy both in vitro and in vivo, as well as exacerbated cardiac remolding induced by pressure overload. Conclusions: In conclusion, our study demonstrates that WTAP is a critical regulator of cardiac function and indicates that appropriate m 6 A RNA methylation is required for cardiac homeostasis.
Abstract 12009: Normal Values and Reference Ranges for Left Atrial Coupling Index: The Copenhagen City Heart Study
Authors: Kirstine Ravnkilde, Kristoffer G Skaarup, Mats H Lassen, Niklas D Johansen, Gorm Jensen, Peter Schnohr, Rasmus Mogelvang, Tor Biering-Srensen
Journal: Circulation (2022)

Introduction: Left atrial volumetric/mechanical coupling index (LACi) has shown increasing clinical and prognostic utility. LACi is a proposed echocardiographic measurement combining information regarding LA size and function in one measure with no established reference values. The aim of the present study was to establish sex-based normative values and a reference range for LACi in the general population. Methods: The present study included healthy participants from the 5th Copenhagen City Heart Study (2011-2015). Participants were considered healthy when free off heart failure, atrial fibrillation, diabetes, hypertension, ischemic heart disease, valvular heart diseases and use of heart medication. All participants were examined with echocardiography. LACi was calculated as the ratio of LA maximal volume index and a’ (peak myocardial velocity of the left ventricle at the septal base in late diastole). Reference values were defined based on prediction intervals (PI) between 2.5% and 97.5%. Results: Among 1,939 participants, mean age was 46 ± 16 years, and 61% were female. Median LACi was 2.5 [95% PI (1.16-4.97)]. We observed higher normative values and reference limits of LACi for females than for males (median 2.5 [95% PI (1.19-5.03)] vs 2.4 [95%PI (1.11- 4.73)], p=0.002) (Figure 1). LACi decreased significantly across age categories for all, and when categorized according to sex. In multivariate linear regression models, younger age (beta=-0.230), female sex (b=-0.081), lower BMI (b=-0.067) and high physical activity (reference: no physical activity during leisure time) (b=0.196) were all significantly associated with higher LACi. Conclusions: We report normative reference values and ranges for LACi in a healthy general population and stratified by sex. LACi was higher in females and decreased with age.
Abstract 11912: Pregabalin Use Increases the Risk of Acute Heart Failure in Patients With Heart Failure: A Population-Based Study
Authors: Emma Wynn, Jospeh Biskupiak, Kibum Kim, Mark A Munger
Journal: Circulation (2022)

Introduction: Pregabalin, a structural analog to λ-aminobutyric acid, is prescribed for neurological disorders. Through actions to cause sodium/water retention, the agent may increase the risk of acute heart failure (AHF). Methods: We performed a retrospective cohort study using a repository of healthcare records obtained from a large U.S. academic healthcare system. HF patients were identified between 1/1/2016-12/31/2020. Patients who had initiated treatment with pregabalin were compared to patients with no post-HF pregabalin over a 365-day post-pregabalin period or post-HF period. Study outcomes were per-patient per-year (PPPY) emergency department (ED) admissions or PPPY hospitalizations, time-to first ED admission, and time-to hospitalizations. Outcomes encounters were adjudicated by a HF diagnosis (ICD-10, I50.x) at any position. We tested the association between the pregabalin exposure and outcomes using generalized linear regression and Cox-proportional hazard regression approach. Results: The study cohort included 483 pregabalin-HF patients and 21,150 pregabalin-naïve HF patients. The pregabalin-HF patients age was (mean±SEM: 62.2±0.7 vs. 66.2±0.1 years, p &lt;0.0001) and more females (54.9% vs, 44.4%, p &lt;0.0001) than pregabalin-naïve HF patients. Charleston comorbidity score was 3.66±0.14 vs. 3.23±0.02 ( p =0.007). Pregabalin use was associated with a 13% increase in PPPY AHF hospitalizations ( p &lt;0.036). A 15% increase in the PPPY ED pregabalin admissions was noted ( p =0.1142). Pregabalin ED admission or AHF hospitalization were 1.492 (95% CI: 1.204 ̶ 1.850 [ p =0.0003]) and 1.112 (95% CI: 0.922 ̶ 1.340 [ p =0.2663]). Conclusion: This retrospective cohort study shows pregabalin is associated with an increased risk of AHF in patients with existing HF. Pregabalin prescribing in HF should be considered with caution. Further signal evaluation to test the robust association between pregabalin and AHF is warranted.
Abstract 12136: Multiple Blood Biomarker Approach for Risk Stratification in Patients With Low-Flow Low-Gradient Aortic Stenosis
Authors: Yassine Abdeldjebbar, Sebastien Hecht, Abdellaziz Dahou, Mohamed-salah Annabi, mathieu bernier, Jonathan Beaudoin, Nancy Cote, Kim OConnor, Eric Larose, Josep Rodes-Cabau, Patrick Mathieu, Marie-Annick Clavel, Philippe Pibarot
Journal: Circulation (2022)

Background and Objectives: Previous studies have shown that a multiple blood biomarker strategy prior to aortic valve replacement (AVR) may be useful for risk stratification in patients undergoing surgical AVR (SAVR). The usefulness of this approach in patients with low-flow low-gradient aortic stenosis (LF-LG AS) has not been examined. The objective of this study was to determine the prognostic value of combined measures of multiple blood biomarkers in patients with LF-LG AS treated conservatively or by AVR. Methods: 168 patients were prospectively enrolled in the TOPAS (Truly or Pseudo-severe Aortic Stenosis) study at our institute. Clinical and echocardiographic data were collected for each patient. Eight biomarkers of myocardial stress, inflammation, renal function (brain natriuretic peptide, creatine kinase-mb, interleukin-6, alanine transaminase, lactate dehydrogenase, alkaline phosphatase, procalcitonin, ferritin) were measured from blood samples collected at baseline. The cohort was divided into 3 groups according to the number of elevated biomarkers. Uni- and multivariable survival analyses were performed to evaluate the association between the number of elevated biomarkers and all-cause mortality. Results: Mean age was 73 years (68% male). After a median follow-up of 3.41 years, 69 (35%) patients died. Patients with 0-3, 4-6, and &gt;6 elevated biomarkers had 8 years survival estimates of 75%, 52%, and 19%, respectively (log-rank p&lt;0.0001). Using multivariable Cox analysis adjusted for age, sex, BMI, AVR as a time-dependent variable, renal function and STS score, patients with &gt;6 elevated biomarkers had an increased risk of all-cause mortality as compared to the group of patients with 0-3 elevated biomarkers (referent group), HR=3.82, p&lt;.0001, and as compared to the group of patients with 4-6 elevated biomarkers HR=2.81, p&lt;.0001. There was no significant difference in all-cause mortality between patients with 4-6 elevated biomarkers and the referent group p=0.38. Conclusion: In this series of patients with LF-LG AS, a higher number of elevated biomarkers was associated with an increased rate of mortality. These results suggest that a multiple blood biomarkers approach may be useful to enhance the risk stratification in this cohort.
Abstract 11615: The Prevalence and Association of Exercise Test Abnormalities With Sudden Cardiac Death and Transplant-Free Survival in Childhood Hypertrophic Cardiomyopathy
Authors: Jennifer Conway, Sandar Min, Chet Villa, Robert G Weintraub, Stephanie J Nakano, Justin Godown, Armstrong Kathyrn, Marc E Richmond, Beth D Kaufman, Ashwin K Lal, Seshadri Balaji, Alyssa Power, Letizia Gardin, Paul F Kantor, John J Parent, Peter F Aziz, John L Jefferies, Tanya Papaz, Aamir Jeewa, Lee N Benson, Mark W Russell, Robert Whitehall, Joseph Rossano, Taylor Howard, Seema Mital
Journal: Circulation (2022)

Introduction: Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, an abnormal exercise stress test (EST) is predictive of heart failure outcomes. Our goal was to determine if an abnormal exercise response is associated with adverse outcomes in pediatric HCM patients. Methods: : In an international cohort study with 20 centers (PRIMaCY), children &lt;18 years with primary HCM were included. Abnormal EST was defined as an abnormal heart rate or blood pressure response, arrhythmias and/or ischemic ECG changes on exercise. Sudden cardiac death (SCD) events were defined as a composite of SCD and aborted SCD including appropriate implantable cardioverter defibrillator discharges. Using Kaplan-Meier survival analyses, we analyzed the association of abnormal EST with SCD and transplant-free survival. Results: Of 724 eligible patients, 604 underwent at least one EST on follow-up. There were no differences in clinical characteristics between those with or without an EST. The median age at EST was 13.8yrs (IQR 11.0-15.7yrs), 76% were male, 55% were on beta-blockers. 299 (49.5%) had an abnormal EST. Patients with an abnormal EST had more severe septal hypertrophy, higher left atrial diameter z-scores, higher resting LV outflow gradient at first evaluation, and a higher proportion were genotype-positive (p&lt;0.05) compared to those with a normal EST. An abnormal EST was associated with lower 5-year transplant-free survival (99% vs. 95%, p=0.0082) and lower 5-year freedom from SCD events (96% vs. 92%, p=0.025) (Figure 1). Conclusions: Exercise abnormalities are common in childhood HCM. An abnormal EST in children with HCM was associated with lower transplant-free survival and more SCD events. Further analysis will determine if the inclusion of EST results can increase the predictive accuracy of current pediatric SCD risk prediction models.
Abstract 12635: Mortality Risks and Need For Transplant in Pediatric Heart Disease Associated With Lower Ses and Greater Remoteness of Residence From Cardiac Care
Authors: Jennifer Conway, Christopher Smith, Douglas C Dover, Andrew Mackie, Andrew S Mackie, Padma Kaul, Lisa K Hornberger
Journal: Circulation (2022)

Introduction: Socioeconomic status (SES) and remoteness of residence (RoR) may contribute to worse clinical outcomes. Whether this is true in universal healthcare is not certain. We sought to explore associations between SES and RoR, from centralized pediatric cardiac care, and a composite of mortality and need for transplant (Tx) in children with congenital (CHD) and acquired heart disease (AHD). Methods: All infants born in Alberta, Canada between 01/01/05 and 31/12/17, and diagnosed before 31/12/17 were included. CHD was categorized as mild, moderate or severe based on the Bethesda Task Force. AHD included cardiomyopathy, myocarditis, heart failure, rheumatic heart disease and endocarditis. Socioeconomic status (SES) was defined by the Canadian Index of Multiple Depravation’s vulnerability index and RoR was calculated using the drive time to one of two pediatric cardiology centers. Risk factors for a composite of mortality and Tx were explored using Cox proportional hazard regression. Results: Among 12,542 children, 74.5% (n=9347) had mild CHD, 13.8% (n=1733) moderate, 5.7% (n=717), severe and 5.9% (n=745) AHD. The composite outcome was highest in severe CHD (19.0%), compared to 13.0% in moderate, 0.5% for mild and 6.9% in AHD, with n=41 undergoing Tx. Among children with CHD, RoR (&gt;180mins, p=0.018), but not SES, was associated with all-cause mortality/Tx (Table 1), while neither RoR (p=0.73) nor SES (p=0.98) were associated with cardiovascular (CV)-specific mortality/Tx. For AHD there was no association between RoR (p=0.73) and SES (p=0.98) with all-cause mortality/Tx (Table 1). Conclusions: Despite Canada’s universal healthcare, children with CHD who live remotely are at increased risk of all-cause mortality/Tx. This is independent of SES and was not true for children with AHD or CV mortality/Tx in those with CHD. Therefore, further understanding of the causes of death in children who live remotely with CHD may help in improving overall outcomes.
Abstract 12664: Comprehensive Histological Analysis of Endomyocardial Biopsy and T1 Mapping for Predicting Left Ventricular Reverse Remodeling in Patients with Recent-Onset Dilated Cardiomyopathy
Authors: Mizuki Ida, Shiro Nakamori, Junko Ishiura, Rie Ito, Masaki Ishida, Naoki Fujimoto, Ryuji Okamoto, Kyoko Imanaka-yoshida, Hajime Sakuma, Kaoru Dohi
Journal: Circulation (2022)

Background: Cardiomyocyte injury is a key pathological pathway in the progression of heart failure that predicts a poor prognosis; therefore, combined assessment of myocardial fibrosis and cardiomyocyte DNA damage from endomyocardial biopsy (EMB) samples may be of great importance. Meanwhile, cardiovascular magnetic resonance (CMR) native T1 reflects a composite of both intra- and extracellular compartments in the whole myocardium. We sought to assess the performance of native T1 mapping and EMB results to predict left ventricular reverse remodeling (LVRR) in recent-onset dilated cardiomyopathy (DCM). Methods: A total of 29 patients with DCM underwent cine CMR and triple-slice T1 mapping using the MOLLI sequence at 3T, and EMB before receiving guideline-directed medical therapy. Poly ADP-ribose (PAR) nuclear and sirius-red staining were used for quantification of DNA damage and collagen volume fraction (CVF), respectively. LVRR was defined as an increase in LV ejection fraction of ≥10% to the final value of &gt;35%, accompanied by a decrease in LV end-diastolic volume ≥10% at the follow-up CMR. Results: Fifteen patients (52%) achieved LVRR. The mean native T1, histological CVF, and proportion of PAR-positive nuclei were 1376 ± 55 ms, 0.13 ± 0.05, 25 ± 15%, respectively. Native T1 correlated well with CVF (p=0.004) and trended to be higher in DCM patients with increased DNA damage (p=0.17). There was no significant association between CVF and %PAR-positive nuclei. Native T1 &lt;1400 ms provided 86% sensitivity and 67% specificity, with the C-statistic of 0.82 (95% CI 0.67-0.98) for predicting LVRR. By contrast, C-statistic of %PAR nuclei, CVF, and combined assessment of %PAR nuclei and CVF were 0.59, 0.61 and 0.66, respectively. Conclusion: CMR T1 mapping may be a promising strategy for noninvasive biopsy of the whole heart and provide a better prediction of LVRR in recent-onset DCM than comprehensive histological analysis of EMB.
Abstract 12220: Right Bundle Branch and Bifascicular Blocks: Insensitive Prognostic Indicators for Acute Myocardial Infarction
Authors: Graham Rector, Jeffrey Triska, Ann Wang, Faris Haddadin, George Ajene, mahboob alam, Yochai Birnbaum
Journal: Circulation (2022)

Introduction: The clinical significance of right bundle branch block (RBBB) or bifascicular block (BFB) in the setting of ST-elevation myocardial infarction (STEMI) is uncertain. Informed by studies demonstrating higher rates of complete occlusion of the infarct-related artery in patients presenting with RBBB, the latest guidelines on STEMI management suggest patients with persistent ischemic symptoms and RBBB be considered for emergent coronary angiography. However, there has been little study of the prognostic implication of either RBBB or BFB in the setting of undifferentiated acute chest pain, and even less of the degree of ST-elevation in concomitant RBBB. Methods and Results: A total of 7626 patient encounters presenting to the Baylor St. Luke’s Medical Center between July 2018 and July 2020 with a chief complaint of “chest pain” were identified via electronic health record query. Of these encounters, 211 (2.8%) patients were found to have RBBB. Of that cohort, 18 (8.5%) presented with acute coronary syndrome, with STEMI accounting for 6 (2.8%), non-STEMI 9 (4.3%), and unstable angina 3 (1.4%). New or presumed new RBBBs were found in 59 (28%) of total RBBB patients, of which only 5 (8.5%) were found to have acute coronary syndrome and only 2 (3.4%) STEMI specifically. Similarly, 90 (42.7%) patients with chest pain and RBBB were found to have a BFB. New or presumed new BFBs were found in 40 (19%) patients, of which only 4 (10%) were also found to have acute coronary syndrome. No patients with new-onset BFB had STEMI. Furthermore, real-time diagnosis of anterior STEMI was complicated in two patients presenting with acute coronary syndrome by the masking of ST elevation in leads V1-3 by concomitant RBBB. Conclusions: In a large cohort of undifferentiated patients who presented with chest pain and RBBB or BFB (regardless if new or presumed new), only a small fraction had acute coronary syndrome, and even fewer STEMI. These data suggest patients with undifferentiated chest pain and RBBB on ECG with clinical suspicion for acute myocardial infarction and any degree of ST-elevation in leads V1-3 be considered for emergent coronary angiography rather than RBBB or BFB without ST-segment elevation.
Abstract 11742: Regional Disparities in Major Adverse Cardiac and Cerebrovascular Events During Hospitalizations in Young (18-44 Years) Obese Patients, 2019 National Inpatient Sample Analysis
Authors: Avilash Mondal, Nanush Damarlapally, Birgurman Singh, Dr. Vaishnavi Arote, Mounika Reddy Vadiyala, Pranjali Singh, Nishtha Rana, Gokul Paidi, Rineetha Tandra, Hardik Patel, Rupak Desai
Journal: Circulation (2022)

Background: Inpatient outcomes in obese patients have been investigated, although regional inequalities in cardiac and cerebrovascular events in young obese patients have not been explored previously. Methods: The National Inpatient Sample 2019 was queried for young obese patients (18-44 years) in 4 regions (Northeast, Midwest, South, West) using ICD-10-CM codes. Baseline characteristics and comorbidities inpatient MACCE including all-cause mortality, AMI, cardiac arrest, and stroke were identified. Results: Young obese cohort (Total n: 1,285,775, median age: 33 years, females: 75.4%) often consisted of admissions in the South (41.1%), followed by the Midwest (22.3%), West (20.7%), and Northeast (20.7%). HTN and DM were more frequent in the Midwest (32.3% and 22.3%) and South (34.4% and 22.8%) respectively, with higher MACCE of South (3.3%) and Midwest (3%) as compared to Northeast (2.3%) and West (2.6%) regions. All regions had comparable median hospital stay (3 days); however, the admissions in the West and Northeast regions (USD 36861 and 31211) had a higher cost burden. After adjusting for sociodemographic and comorbidities, the odds of in-hospital MACCE were higher in the West (aOR 1.15 95%CI 1.02-1.29), and South (aOR 1.16 95%CI 1.04-1.29), (p&lt;0.001) vs. Northeast admissions (Fig. 1) . Conclusion: Cardiovascular comorbidities and MACCE were higher in young obese admissions in the South. This disparity may be due to differences in behavioral risk factors, socioeconomic status and healthcare access/prices. Future prospective studies on regional differences can help identify high-risk young, obese populations for targeted screening.